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Growth Regulation of Human Renal Carcinoma Cells: Role of Transforming Growth Factor ¹

Laboratory of Receptor Biology [I. A., J. M., J. B., H. M., R. K.] and Division of Urology [I. A., W. R. F.], Memorial Sloan-Kettering Cancer Center, and Cornell University Medical College [J. M., W. R. F.], New York, New York 10021

Findings of increased numbers of epidermal growth factor receptors (EGF-R) and increased expression of transforming growth factor (TGF-) in surgical specimens of human renal cell carcinoma have led to the proposal that growth of these tumors may be regulated by TGF- in an autocrine manner. In the studies presented here, we have examined this hypothesis using two human renal carcinoma cell lines, SKRC-4 and SKRC-29. We demonstrated that both SKRC-4 and SKRC-29 cells were growth stimulated by >35% when cultured in the presence of TGF- or EGF and were inhibited by 29% to 46% if cultured in the presence of anti-EGF-R monoclonal antibody 225. Treatment of cells with TGF- enhanced the levels of expression of EGF-R mRNA and TGF- mRNA. In addition, incubation of cells with monoclonal antibody 225 significantly elevated the levels of excreted TGF- species in the culture medium. Our findings suggest that proliferation of human renal carcinoma cells may be regulated by endogenously produced TGF- and that this regulatory pathway can be interrupted using antibody to its receptor, EGF-R.

¹ This work was supported by Grants CA-42060 and CA-37641 from the NIH. I. A. is a recipient of a research fellowship from the National Kidney Foundation of New York and New Jersey.

² To whom requests for reprints should be addressed, at Laboratory of Receptor Biology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021.

Received 6/24/91. Accepted 4/ 7/92.

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